Hepatitis A is an acute illness characterized by sudden onset of fever, malaise, nausea, anorexia, and abdominal discomfort, followed in several days by jaundice. Hepatitis A is the most common type of hepatitis reported in the United States, which reports an estimated 134,000 cases annually, and infects at least 1.4 million people worldwide each year (Source: Cohn & Wolfe Healthcare, Hepatitis Information Network website).
The causative agent of hepatitis A is the liver-infecting hepatitis A virus (HAV), which is a positive sense RNA virus that is transmitted via the fecal-oral route, mainly through contaminated water supplies and food sources. Hepatitis A virus is a member of the family Picornaviridae. HAV is thought to replicate in the oropharynx and epithelial lining of the intestines, where it initiates a transient viremia and subsequently infects the liver.
Humoral immunity has been shown to provide an effective defense against hepatitis A. Prior to the availability of the current inactivated virus vaccines, pooled human immune globulin preparations were routinely used to protect individuals traveling to areas of the world where hepatitis A is endemic (See Hollinger and Emerson, Hepatitis A Virus, 4th ed. In “Fields Virology” Vol. 1, 799-840, 2001). Unlike the neutralization of other members of the Picornaviridae, such as poliovirus and human rhinovirus, very little is understood about the mechanism of antibody-mediated neutralization of HAV. This is despite the fact that some strains of the virus grow in cell culture, albeit much less efficiently than do other picornaviruses.
The hepatitis A virion is an icosahedron comprised of pentamers of three structural proteins, VP1, VP2 and VP3. A fourth structural protein found in other picornaviruses, VP4, is truncated in HAV and has not been identified in virions. Epitopes recognized by the known murine neutralizing antibodies on the HAV capsid are dependent on the conformation of the antigen. Very few neutralizing antibodies have been generated to expressed antigens or subunit proteins.
Because antibodies elicited to HAV may neutralize the infectivity of the virus, the administration of a highly reactive, neutralizing anti-HAV antibody preparation to an individual who is at risk of infection, or who has recently been exposed to the infectious agent, would be of use in providing passive immunity to the immunized individual. Thus, there is a need for antibodies directed against HAV that may be used to protect individuals at risk for HAV infection or who have recently been exposed to HAV.